β-Lactoglobulin Is Insulinotropic Compared with Casein and Whey Protein Ingestion during Catabolic Conditions in Men in a Double-Blinded Randomized Crossover Trial

Abstract

Background Muscle loss during acute infectious disease is mainly triggered by inflammation, immobilization, and malnutrition. Objective The objective was to compare muscle protein kinetics and metabolism following ingestion of the dairy protein supplements β-lactoglobulin (BLG), casein (CAS), and whey (WHE) during controlled catabolic conditions. Methods We used a randomized crossover design (registered at clinicaltrials.gov as NCT03319550) to investigate 9 healthy male participants [age: 20–40 y; BMI (in kg/m2) 20–30] who were randomly assigned servings of BLG, CAS, or WHE (0.6 g protein/kg, one-third as bolus and two-thirds as sip every 20 min) on 3 separate occasions separated by ∼6–8 wk. The participants received an infusion of lipopolysaccharide (1 ng/kg) combined with 36 h of fasting and bed rest before each study day, mimicking a clinical catabolic condition. The forearm model and isotopic tracer techniques were used to quantify muscle protein kinetics. Muscle biopsy specimens were obtained and intramyocellular signaling investigated using Western blot. Results BLG, CAS, and WHE improved the net balance of phenylalanine (NBphe) from baseline with ∼75% (P < 0.001) with no difference between interventions (primary outcome, P < 0.05). No difference in rates of appearance and disappearance of phenylalanine or in intramyocellular signaling activation was found between interventions (secondary outcomes). The incremental AUC for serum insulin was 62% higher following BLG compared with CAS (P < 0.001) and 30% higher compared with WHE (P = 0.002), as well as 25% higher in WHE compared with CAS (P = 0.006). Following BLG consumption, plasma concentrations of glucose-dependent insulinotropic peptide (GIP) increased 70% compared with CAS (P = 0.001) and increased 34% compared with WHE (P = 0.06). No significant difference was found between WHE and CAS (P = 0.12). Conclusion BLG, WHE, and CAS have similar effects on muscle in young male participants during catabolic conditions. BLG showed specific, possibly GIP-dependent, insulinotropic properties, which may have future clinical implications.

The effect of combined β-lactoglobulin supplementation and resistance exercise training prior to limb immobilisation on muscle protein synthesis rates in healthy young adults: study protocol for a randomised controlled trial

“…The biological rationale for administering β-lactoglobulin supplementation in the present study is underpinned by two primary lines of evidence. First, β-lactoglobulin exhibits an exceptionally high leucine content (16%) that exceeds the constituent leucine profile (~ 12%) of whey protein [ 21 ]. In addition to providing substrate for the synthesis of new muscle protein, leucine also acts a signalling molecule to trigger MPS via activation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway [ 1 , 2 ].…”

“…A secondary rationale for β-lactoglobulin supplementation relates to the marked insulinotropic response and associated direct and/or indirect action of insulin on MPS. In this regard, the serum insulin AUC following β-lactoglobulin ingestion was 62% higher than casein and 30% higher than whey and corresponded with a higher plasma glucose-dependent insulinotropic peptide response [ 21 ]. In the presence of exogenous amino acids, insulin has been shown to stimulate MPS via the direct activation of mTORC1 signalling [ 6 , 16 , 24 ].…”

The effect of combined β-lactoglobulin supplementation and resistance exercise training prior to limb immobilisation on muscle protein synthesis rates in healthy young adults: study protocol for a randomised controlled trial

“…Protocol version: 16-12-2022 / 1 Background β-lactoglobulin is a novel milk protein with an exceptionally high leucine content. Over 16% of βlactoglobulin consists of leucine which exceeds the constituent leucine content of whey protein that contains 12% leucine (Mose et al, 2021). Dietary supplementation with proteins that are rich in leucine has been shown to stimulate increased rates of muscle protein synthesis (MPS) via activation of the mechanistic target of rapamycin (mTOR) pathway (Anthony et al, 1999;Anthony et al, 2002).…”